The purposes of the proposed work are: 1. To determine conditions of minimal chain scission consistent with maximal labelling and base pairing fidelity for the TlCl3 catalyzed in vitro iodination of DNA. Conditions will be determined where labelled and renatured restriction fragments of DNA may be used to replace in vivo labelled fragments. 2. To determine conditions for the optimal utilization of the foreign polymer excluded volume effect which leads to acceleration of DNA renaturation reactions. A quantitative method will be developed for predicting these acceleration effects. 3. To investigate the effect of the alternation of repeated DNA and single copy DNA sequences on renaturation kinetics analyses in mammalian systems through use of temperature pulsed renaturation in 2.4M tetraethylammonium chloride. The results will be related to the evolution and organization of eukaryotic chromosomes. 4. To investigate the interaction between E. coli K12 unwinding protein and DNA. This study will include the effect of this protein on the cyclization of lambda DNA. 5. To develop the method of kinetic extraction of genetically defined DNA fragments. This gene isolation method will be applied to Drosophila melanogaster where the isolated products may be mapped by in situ hybridization. BIBLIOGRAPHIC REFERENCES: "Hybridization and Renaturation Kinetics of Nucleic Acids," J. G. Wetmur, Ann. Rev. Biophys. Bioeng. 5:337 (1976). "Studies on the Non-Cooperative Binding of the Escherichia coli DNA Unwinding Protein to Single-Stranded Nucleic Acids," W. T. Ruyechan and J.G. Wetmur, Biochem. 15:5057 (1976).